Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease

Adriana Huertas-Vazquez; Christopher P. Nelson; Xiuqing Guo; Kyndaron Reinier; Audrey Uy-Evanado; Carmen Teodorescu; Jo Ayala; Katherine Jerger; Harpriya Chugh; WTCCC+; Peter S. Braund; Panos Deloukas; Alistair S. Hall; Anthony J. Balmforth; Michelle Jones; Kent D. Taylor; Sara L. Pulit; Christopher Newton-Cheh; Karen Gunson; Jonathan Jui; Jerome I. Rotter; Christine M. Albert; Nilesh J. Samani; Sumeet S. Chugh; Craig Mowat

doi:10.1371/journal.pone.0059905

Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease

Adriana Huertas-Vazquez, Christopher P. Nelson, Xiuqing Guo, Kyndaron Reinier, Audrey Uy-Evanado, Carmen Teodorescu, Jo Ayala, Katherine Jerger, Harpriya Chugh, WTCCC+, Peter S. Braund, Panos Deloukas, Alistair S. Hall, Anthony J. Balmforth, Michelle Jones, Kent D. Taylor, Sara L. Pulit, Christopher Newton-Cheh, Karen Gunson, Jonathan JuiJerome I. Rotter, Christine M. Albert, Nilesh J. Samani (Lead / Corresponding author), Sumeet S. Chugh (Lead / Corresponding author), Craig Mowat (Research group member)

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Abstract

BACKGROUND: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).

METHODS AND FINDINGS: Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8), OR = 2.41).

CONCLUSIONS: Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.

Original language	English
Article number	e59905
Number of pages	6
Journal	PLoS ONE
Volume	8
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0059905
Publication status	Published - 4 Apr 2013

Keywords

Adult
Aged
Case-Control Studies
Coronary Artery Disease/complications
DNA-Binding Proteins/genetics
Death, Sudden, Cardiac/etiology
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Introns
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk
Transcription Factors/genetics
rab3 GTP-Binding Proteins/genetics

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Huertas-Vazquez, A., Nelson, C. P., Guo, X., Reinier, K., Uy-Evanado, A., Teodorescu, C., Ayala, J., Jerger, K., Chugh, H., WTCCC+, Braund, P. S., Deloukas, P., Hall, A. S., Balmforth, A. J., Jones, M., Taylor, K. D., Pulit, S. L., Newton-Cheh, C., Gunson, K., ... Mowat, C. (2013). Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease. PLoS ONE, 8(4), Article e59905. https://doi.org/10.1371/journal.pone.0059905

@article{cd780006c6184d499c7e062a5bef4e06,

title = "Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease",

abstract = "BACKGROUND: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).METHODS AND FINDINGS: Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8), OR = 2.41).CONCLUSIONS: Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.",

keywords = "Adult, Aged, Case-Control Studies, Coronary Artery Disease/complications, DNA-Binding Proteins/genetics, Death, Sudden, Cardiac/etiology, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Introns, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Transcription Factors/genetics, rab3 GTP-Binding Proteins/genetics",

author = "Adriana Huertas-Vazquez and Nelson, {Christopher P.} and Xiuqing Guo and Kyndaron Reinier and Audrey Uy-Evanado and Carmen Teodorescu and Jo Ayala and Katherine Jerger and Harpriya Chugh and WTCCC+ and Braund, {Peter S.} and Panos Deloukas and Hall, {Alistair S.} and Balmforth, {Anthony J.} and Michelle Jones and Taylor, {Kent D.} and Pulit, {Sara L.} and Christopher Newton-Cheh and Karen Gunson and Jonathan Jui and Rotter, {Jerome I.} and Albert, {Christine M.} and Samani, {Nilesh J.} and Chugh, {Sumeet S.} and Craig Mowat",

year = "2013",

month = apr,

day = "4",

doi = "10.1371/journal.pone.0059905",

language = "English",

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issn = "1932-6203",

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Huertas-Vazquez, A, Nelson, CP, Guo, X, Reinier, K, Uy-Evanado, A, Teodorescu, C, Ayala, J, Jerger, K, Chugh, H, WTCCC+, Braund, PS, Deloukas, P, Hall, AS, Balmforth, AJ, Jones, M, Taylor, KD, Pulit, SL, Newton-Cheh, C, Gunson, K, Jui, J, Rotter, JI, Albert, CM, Samani, NJ, Chugh, SS & Mowat, C 2013, 'Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease', PLoS ONE, vol. 8, no. 4, e59905. https://doi.org/10.1371/journal.pone.0059905

TY - JOUR

T1 - Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease

AU - Huertas-Vazquez, Adriana

AU - Nelson, Christopher P.

AU - Guo, Xiuqing

AU - Reinier, Kyndaron

AU - Uy-Evanado, Audrey

AU - Teodorescu, Carmen

AU - Ayala, Jo

AU - Jerger, Katherine

AU - Chugh, Harpriya

AU - WTCCC+

AU - Braund, Peter S.

AU - Deloukas, Panos

AU - Hall, Alistair S.

AU - Balmforth, Anthony J.

AU - Jones, Michelle

AU - Taylor, Kent D.

AU - Pulit, Sara L.

AU - Newton-Cheh, Christopher

AU - Gunson, Karen

AU - Jui, Jonathan

AU - Rotter, Jerome I.

AU - Albert, Christine M.

AU - Samani, Nilesh J.

AU - Chugh, Sumeet S.

A2 - Mowat, Craig

PY - 2013/4/4

Y1 - 2013/4/4

N2 - BACKGROUND: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).METHODS AND FINDINGS: Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8), OR = 2.41).CONCLUSIONS: Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.

AB - BACKGROUND: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).METHODS AND FINDINGS: Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8), OR = 2.41).CONCLUSIONS: Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.

KW - Adult

KW - Aged

KW - Case-Control Studies

KW - Coronary Artery Disease/complications

KW - DNA-Binding Proteins/genetics

KW - Death, Sudden, Cardiac/etiology

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Humans

KW - Introns

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk

KW - Transcription Factors/genetics

KW - rab3 GTP-Binding Proteins/genetics

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U2 - 10.1371/journal.pone.0059905

DO - 10.1371/journal.pone.0059905

M3 - Article

C2 - 23593153

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 4

M1 - e59905

ER -

Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease

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Keywords

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